Desflurane

Article Author:
Joohi Khan
Article Editor:
Mark Liu
Updated:
10/2/2019 9:09:41 AM
PubMed Link:
Desflurane

Indications

The FDA-approved indications for desflurane are induction or maintenance of anesthesia in adults. It may also be used for maintenance of anesthesia in pediatric patients following induction with agents other than desflurane. Desflurane is a racemic mixture of two enantiomers. Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) was first synthesized in the 1970s, it is halogenated exclusively with fluorine, and is very resistant to defluorination.[1] For this reason, it is not associated with nephrotoxicity, as is the case with other inhalational anesthetic agents.  When first introduced, desflurane was difficult to synthesize and expensive, limiting its use, but given its low blood solubility and rapid induction, it became more popular. It has the most rapid onset of the inhalational anesthetics, but the higher cost of desflurane limits its use compared to other agents.

Mechanism of Action

The mechanism of action of the inhalational agents is still unclear. Inhalational anesthetics are thought to work via interaction with different ion channels that are present throughout the central and peripheral nervous system, by blocking excitatory channels and enhancing the activity of inhibitory channels. Other proposed mechanisms are that these agents work by affecting the membrane bilayer. The structure of desflurane is similar to that of isoflurane except for the addition of a fluorine atom. This addition changes the physical properties of desflurane compared to other inhalational agents. The vapor pressure of desflurane at 20 degrees Celsius is 681 mm Hg, with a boiling point of 22.8 degrees Celsius. Desflurane requires the use of a temperature controlled, pressure regulated vaporizer, as opposed to variable bypass vaporizer. The molecular weight of desflurane is 168 grams, and a very small percentage of the anesthetic is metabolized by the body, in comparison to other inhalational agents.

Administration

Desflurane administration is via the inhalational route. It has a pungent odor, making it difficult to use for the induction of general anesthesia. It is used most commonly for maintenance of general anesthesia after induction with an IV or another inhalational agent. Minimal alveolar concentration (MAC) of desflurane is 6.0% in the 31-65 year age group, and 7.25% in the 18-30 year age group. The blood/gas partition coefficient of desflurane is 0.42, making it even less soluble than nitrous oxide which has a blood/gas partition coefficient of 0.47. Desflurane can cause very rapid induction and emergence from anesthesia given its low blood solubility. This quality allows the alveolar concentration to approach the inspired concentration of desflurane much more quickly, permitting rapid titration of anesthetic levels. Emergence with desflurane after an hour-long case can take around six minutes, in contrast to sevoflurane which can take up to 18 minutes. Desflurane's vapor pressure, 681mm Hg at sea level, is significantly higher than the other inhalational anesthetics and leads to a boiling point near room temperature. Its high vapor pressure and low boiling point led to the creation of a special desflurane vaporizer. This vaporizer pressurizes desflurane to 1500 mm Hg, which is roughly two atmospheres of pressure and warms it to 40 degrees Celsius, allowing optimal control of the concentration of anesthetic delivered to the patient. Desflurane vaporizers are electrically powered heat devices.

Adverse Effects

Desflurane, along with the other inhalational agents, sevoflurane and isoflurane, is a potent vasodilator and can cause a decrease in blood pressure by decreasing systemic vascular resistance (SVR). A concomitant increase in heart rate sometimes occurs. Cardiac output is typically preserved with the use of this agent. Desflurane dilates cerebral arteries and causes a decrease in cerebral metabolic rate. Desflurane also causes an increase in intracranial pressure (ICP), like other inhalational anesthetics. This increase in ICP can be targeted by hyperventilation and hypocapnia in a patient as carbon dioxide (CO2) autoregulation is maintained with use. There is also a dose-related depression in electroencephalogram (EEG) activity with the use of desflurane.  When used for the maintenance of anesthesia in the pediatric population, after induction with another inhalational agent, desflurane was associated with an increased rate of emergence delirium.

Rapid increases in the concentration of desflurane can cause a transient but clinically significant elevation in heart rate and blood pressure. These effects are secondary to catecholamine release, which is more pronounced with desflurane than isoflurane or sevoflurane. This resulting sympathetic response is controllable by concurrent administration of esmolol, clonidine, or use of an opioid. Slowing the rate of increase in the concentration of desflurane can also decrease the catecholamine release. Volatile anesthetics promote skeletal muscle relaxation and enhance the effects of neuromuscular blocking agents. Desflurane enhances the effects of rocuronium, greater than either sevoflurane, isoflurane or intravenous anesthetics. As with all inhaled anesthetics, there is a decrease in the ventilatory response to CO2.[2]

Contraindications

Desflurane contraindications include induction of anesthesia in nonintubated pediatric patients because of a high incidence of moderate to severe upper airway adverse events. Pediatric patients are at high risk of laryngospasm[3]. Desflurane is also contraindicated in patients with known or suspected susceptibility to malignant hyperthermia. If the patient has a history of moderate to severe hepatic impairment following general anesthesia with desflurane, use of desflurane should be avoided. Additionally, if a patient has intracranial hypertension, desflurane is contraindicated, as is the case with all such volatile agents.[4]

Monitoring

Neurologic monitoring has been used to assess for depth of anesthesia in the operating room setting. Electroencephalogram (EEG) is infrequently used during cerebrovascular surgery to monitor anesthesia and cerebral oxygenation. Most commonly used is a bispectral index (BIS) to indicate wakefulness in a patient.[5] BIS levels of 65-85 have been advocated as a measure of sedation, whereas values of 40-65 are the recommendation for general anesthesia; this is a measure that is used to reduce patient conscious awareness.[5] Standard American Society of Anesthesiologists (ASA) monitors are required when the administration of desflurane is ongoing.

Toxicity

Desflurane is the most likely inhaled anesthetic to result in carbon monoxide (CO) production, compared with isoflurane and sevoflurane. The mechanism of production of CO is through degradation of desflurane by desiccated CO2 absorbent, barium hydroxide lime, and can produce clinically significant levels of carbon monoxide, stressing the importance of replacing dried CO2 absorbent. Although rare, severe hepatic injury can follow anesthesia with desflurane, along with other inhalational agents, and may include massive hepatic necrosis. The mechanism is immunologic. Desflurane undergoes metabolism by cytochrome P-450 to produce trifluoroacetate, which binds to hepatocyte proteins, forming complexes that will stimulate antibody formation. Exposures after antibody formation can lead to hepatic necrosis. This is much less common than with other agents such as halothane, but is still possible, given the metabolite. There is currently no treatment for hepatic effects of desflurane; use of desflurane or similar inhalational anesthetics should be avoided in the future if any hepatic impairment is suspected.[6]

Enhancing Healthcare Team Outcomes

Interprofessional communication is vital in preventing any untoward effects from desflurane. The earlier identification of the signs and symptoms of a complication occurs, the better is the prognosis and outcome. The anesthesiologist must make the surgeon aware and all other staff in the operating room if any complication is suspected. One particular example is in the case of malignant hyperthermia; given the high-risk outcome of patients with suspected malignant hyperthermia, corrective action must take place immediately. Offending agents must be discontinued, and immediate enactment of treatment algorithms for malignant hyperthermia should supersede continuation of the surgical procedure until the restoration of hemodynamic stability.


References

[1] Tuncal? B,Pekcan Y�,Ayhan A,Erol V,Y?lmaz TH,Kayhan Z, Retrospective Evaluation of Patients who Underwent Laparoscopic Bariatric Surgery. Turkish journal of anaesthesiology and reanimation. 2018 Aug     [PubMed PMID: 30140537]
[2] Liu Q,Ma L,Fan SZ,Abbod MF,Ai Q,Chen K,Shieh JS, Frontal EEG Temporal and Spectral Dynamics Similarity Analysis between Propofol and Desflurane Induced Anesthesia Using Hilbert-Huang Transform. BioMed research international. 2018     [PubMed PMID: 30112395]
[3] Jain A,Gombar S,Ahuja V, Recovery Profile After General Anaesthesia in Paediatric Ambulatory Surgeries: Desflurane Versus Propofol. Turkish journal of anaesthesiology and reanimation. 2018 Feb     [PubMed PMID: 30140497]
[4] Gabellini G,Graziano A,Carron M, Hepatotoxicity after desflurane anesthesia in a morbidly obese patient. Journal of clinical anesthesia. 2018 Dec     [PubMed PMID: 30096519]
[5] Yu H,Zhang L,Ma Y,Yu H, Early postoperative recovery in operating room after desflurane anesthesia combined with Bispectral index (BIS) monitoring and warming in lengthy abdominal surgery: a randomized controlled study. BMC anesthesiology. 2018 Aug 17     [PubMed PMID: 30115007]
[6] Desflurane null. 2006     [PubMed PMID: 30000560]